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转录激活缺陷型c-MycS保留调节增殖和凋亡的能力。

Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis.

作者信息

Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J, Hann S R

机构信息

Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175 USA.

出版信息

Genes Dev. 1998 Dec 15;12(24):3803-8. doi: 10.1101/gad.12.24.3803.

DOI:10.1101/gad.12.24.3803
PMID:9869633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC317265/
Abstract

Transcriptional activation by c-Myc through specific E box elements is thought to be essential for its biological role. However, c-MycS is unable to activate transcription through these elements and yet retains the ability to stimulate proliferation, induce anchorage-independent growth, and induce apoptosis. In addition, c-MycS retains the ability to repress transcription of several specific promoters. Furthermore, c-MycS can rescue the c-myc null phenotype in fibroblasts with homozygous deletion of c-myc. Taken together, our data argue against the paradigm that all of the biological functions of c-Myc are mediated by transcriptional activation of specific target genes through E box elements.

摘要

c-Myc通过特定E盒元件进行的转录激活被认为对其生物学作用至关重要。然而,c-MycS无法通过这些元件激活转录,但仍保留刺激增殖、诱导不依赖贴壁生长和诱导凋亡的能力。此外,c-MycS保留了抑制几个特定启动子转录的能力。此外,c-MycS可以挽救c-myc纯合缺失的成纤维细胞中的c-myc无效表型。综上所述,我们的数据与c-Myc的所有生物学功能都是通过E盒元件对特定靶基因的转录激活来介导的这一范式相悖。

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1
Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis.转录激活缺陷型c-MycS保留调节增殖和凋亡的能力。
Genes Dev. 1998 Dec 15;12(24):3803-8. doi: 10.1101/gad.12.24.3803.
2
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本文引用的文献

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c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets.c-myc基因缺失的细胞会错误调节cad和gadd45,但不会错误调节其他推测的c-Myc靶标。
Genes Dev. 1998 Dec 15;12(24):3797-802. doi: 10.1101/gad.12.24.3797.
2
The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.新型ATM相关蛋白TRRAP是c-Myc和E2F癌蛋白的重要辅助因子。
Cell. 1998 Aug 7;94(3):363-74. doi: 10.1016/s0092-8674(00)81479-8.
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Myc represses transcription of the growth arrest gene gas1.Myc抑制生长停滞基因gas1的转录。
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12886-91. doi: 10.1073/pnas.94.24.12886.
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Myc represses the growth arrest gene gadd45.Myc抑制生长停滞基因gadd45。
Oncogene. 1997 Jun 12;14(23):2825-34. doi: 10.1038/sj.onc.1201138.
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Myc target genes.Myc靶基因。
Trends Biochem Sci. 1997 May;22(5):177-81. doi: 10.1016/s0968-0004(97)01025-6.
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Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.致癌性Ras会引发与p53和p16INK4a积累相关的细胞早衰。
Cell. 1997 Mar 7;88(5):593-602. doi: 10.1016/s0092-8674(00)81902-9.
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Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins.鉴定下游起始的c-Myc蛋白,其为全长c-Myc蛋白反式激活的显性负性抑制剂。
Mol Cell Biol. 1997 Mar;17(3):1459-68. doi: 10.1128/MCB.17.3.1459.
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Proteins of the Myc network: essential regulators of cell growth and differentiation.Myc 网络的蛋白质:细胞生长和分化的重要调节因子。
Adv Cancer Res. 1996;68:109-82. doi: 10.1016/s0065-230x(08)60353-x.
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A novel function for Myc: inhibition of C/EBP-dependent gene activation.Myc的一种新功能:抑制C/EBP依赖性基因激活。
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6635-40. doi: 10.1073/pnas.93.13.6635.